The present study aims to numerically investigate the effect of cross section on the heat transfer performance of single-phase flow of Ethanol/Polyalphaolefin nanoemulsion fluid with ethanol concentrations of 8 wt.% in a microchannel heat exchanger. While the exterior geometry of the microchannels’ solid structure remains the same, four different cross sections of channels including: circular, upward semi-circular, rectangular, and trapezoidal, are designed with keeping the channels’ wetted perimeters, mass flow rate, and Reynolds number constant for comparison purposes. In the present study, the hydrodynamic and heat transfer characteristics, including local Nusselt number, heat transfer coefficient, and velocity profile, were investigated under a uniform wall heat flux boundary conditions within the laminar flow regime. The channel models of different cross sections were developed by the COMSOL-Multiphysics for numerical analysis. The heat transfer characteristics were then compared for different cross sections under the same operating conditions, and the effect of aspect ratio for rectangular and trapezoidal cross sections were also studied.